Toxicity and antimicrobial interactions with conventional antimicrobials of commonly traded medicinal plants from Faraday muthi market (Johannesburg, South Africa)

In South Africa, medicinal plants are frequently used to treat infections, with the Faraday muthi market in Johannesburg ensuring accessibility to these medicines. This study aimed to determine the in vitro interactive antimicrobial and toxicity profiles of commonly traded traditional medicinal plants at the Faraday muthi market, with a range of conventional antimicrobials. Minimum inhibitory concentration (MIC) assays were conducted to determine the in vitro interactive profiles and tested against the ESKAPE pathogens ( Enterococcus faecium ATCC 27270, Staphylococcus aureus ATCC 29212, Klebsiella pneumoniae ATCC 13883, Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, Enterobacter cloacae ATCC 13460) and yeasts, Candida albicans ATCC 10231 and Candida glabrata ATCC 90030. The fractional inhibitory concentration index (ΣFIC) was determined to classify interactions as synergistic, additive, non-interactive or antagonistic. The brine-shrimp lethality assay (BSLA) was conducted to determine the toxicity of synergistic interactions. A total of 816 plant: antibiotic combinations were tested against the ESKAPE pathogens, with 392 combinations exhibiting a definitive ΣFIC. Synergy (6.63 %), antagonism (47.45 %), additive (8.67 %) and non-interactive (37.24 %) profiles were observed. Medicinal plants were most widely synergistic with azithromycin against S. aureus. Hypoxis hemerocallidea with azithromycin against S. aureus (ΣFIC 0.06) was the most synergistic, with no toxicity evident in the BLSA (6.06 % mortality). The most antagonistic interaction was with Eucalyptus sideroxylon and amoxicillin against K. pneumoniae (ΣFIC 138.12). Furthermore, a total of 136 plant: antifungal combinations were tested, where a definitive ΣFIC was obtained for 84 of the combinations. No synergy was observed, but 61.91 % of the combinations were antagonistic. The most antagonistic plant: antifungal combination was observed with Senecio serratuoloides and nystatin against C. albicans (ΣFIC 34.6). The vast antagonism against the ESKAPE pathogens (47.49 %) and yeasts (61.90 %) is cause for concern, particularly with antimicrobial resistance development. The most toxic combinations in the BSLA were when azithromycin was combined with Synaptolepis oliveriana (54.50 % average mortality after 48 h) and with Warburgia salutaris (100 % average mortality after 48 h). The synergy and antagonism observed in this study warrants further investigation for clinical translation, to determine potentially beneficial or harmful combinations where applicable.